SQSTM1/p62 通过诱导细胞周期阻滞和调节免疫细胞浸润来调控乳腺癌进展和转移

The autophagy adaptor protein SQSTM1/p62 is overexpressed in breast cancer and has been identified as a metastasis-related protein.

However, the mechanism by which SQSTM1/p62 contributes to breast cancer progression and tumor microenvironment remains unclear.

This study revealed that silencing SQSTM1/p62 expression suppressed breast cancer progression via regulating cell proliferation and reshaping the tumor microenvironment (TME).

Here, we found that SQSTM1/ p 62 was overexpressed in multiple human cancer tissue types and that was correlated with poor patient overall survival (OS) and disease-free survival (DFS).

Moreover, we found that short-hairpin RNA (shRNA)-mediated knockdown of p62 expression significantly inhibited cell proliferation, migration, and invasion, and promoted cell death in vitro , as well as suppressed breast cancer growth and lung metastasis in vivo .

In addition, flow cytometry analysis of splenocytes and tumor infiltrating lymphocytes (TILs) indicated that the numbers of CD8α + interferon (IFN)-γ + cells (CTLs) and CD4 + IFN-γ + (Th1) cells were increased while those of CD4 + IL-4 + (Th2) cells, tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) were decreased. RT-PCR analyses showed that the gene expression of Th1/Th2 cytokines changed in the tumor microenvironment. Silencing SQSTM1 / p 62 suppressed tumor cell lung metastasis.

Together, our results provide strong evidence that silencing tumor cell SQSTM1 / p 62 inhibited tumor growth and metastasis through cell cycle arrest and TME regulation. This finding provides a novel molecular therapeutic strategy for breast cancer progression and metastasis treatment.